The discovery of the multifaceted role of nitric oxide (NO) in biology, physiology, and pathophysiology, see Marietta, M. A., et al., BioFactors, 2, 219-225 (1990), has led to the search for nitric oxide donors capable of controlled nitric oxide release. See Keefer, L. K., Chemtech, 28, 30-35 (1998). To date, researchers have discovered that NO regulates a range of biological processes in the cardiovascular, gastrointestinal, genitourinary, respiratory, and central and peripheral nervous systems. See Ignarro, L. J., Nitric Oxide: Biology and Pathobiology; Academic Press: San Diego, 2000; and Ignarro, L. J. et al., Proc. Natl. Acad. Sci., U.S.A., 84, 9265-9269 (1987). Furthermore, the discovery of NO as a vasodilator and its identification as both an antibiotic and a tumoricidal factor have made NO an attractive pharmaceutical candidate. See, for example, Radomski, M. W., et al., Br. J. Pharmacol., 92, 639-646 (1987); Albina, J. E., and Reichner, J. S.; Canc. Metas. Rev., 17, 19-53 (1998); Nablo, B. J., at al., J. Am. Chem. Soc., 123, 9712-9713 (2001); Cobbs, C. S., et al., Cancer Res., 55, 727-730 (1995); Jenkins, D. C., at al., Proc. Natl. Acad. Sci., U.S.A., 92, 4392-4396 (1995); and Thomsen, L. L., et al., Br. J. Cancer., 72, 41-44 (1995).
Several nitric oxide donors have been reported, the most notable being N-diazeniumdiolates. Generally, N-diazeniumdiolate NO donors are small molecules synthesized by the reaction of amines with NO at elevated pressure and have been used, for example, to spontaneously generate NO in aqueous solution. See Hrabie, J. A. and Keefer, L. K, Chem. Rev., 102, 1135-1154 (2002).
Therapeutic strategies to explore the activities of nitric oxide donors, for example, to kill tumor cells, are problematic in part because the nitric oxide delivery systems known in the art release or donate nitric oxide indiscriminately. Thus, there is a need in the art for a nitric oxide delivery system that releases or donates nitric oxide in a controlled and/or targeted manner to facilitate an improved understanding of the function of NO in physiology and to provide for the development of NO-associated therapies.